Genome-wide screen for promoter methylation in NSCLC identifies novel methylation markers for multiple malignancies
From ArrayWiki
| PubMed ID: | 17194187 |
|---|---|
| Contact: | David S Shames
|
| Species: | Homo sapiens |
| Platform: | Affymetrix GeneChip Human Genome U133 Plus 2.0 Array |
| Number of Samples: | 7 |
| Date Range: | 01/09/2004 - 08/10/2004 |
| Experiment Quality: | 94.91 6.11 % |
| Link to Repository: | GSE6695 |
| Original Intensity Data: | Download |
| Clean Intensity Data: | Download |
| Original PLIER Data: | Download |
| Clean PLIER Data: | Download |
| Clean CEL Files: | |
| Data Rank: | 
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BACKGROUND: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. METHODS AND FINDINGS: In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5' CpG islands, are induced from undetectable levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. CONCLUSIONS: By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention.
Design: We compared the gene expression changes HBEC and NSCLC cells before and after treatment with 5-aza-2'deoxycytidine.
Type: Dose response, cell-type comparison,
Contents |
[edit] Contributors
- David S Shames
- Luc Girard
- Boning Gao
- Mitsuo Sato
- Cheryl M Lewis
- Narayan Shivapurkar
- Aixiang Jiang
- Charles M Perou
- Young H Kim
- Jon R Pollack
- Kwon M Fong
- Chi-Leung Lam
- Maria Wong
- Yu Shyr
- Rita Nanda
- Olufunmilayo I Olopade
- William Gerald
- David M Euhus
- Jerry W Shay
- Adi F Gazdar
- John D Minna
[edit] Protocols
[edit] References
[edit] Links
GEO Accession for this experiment: GSE6695. (Public on Aug 28 2007)
PubMed abstract: 17194187
RAW data: tar file.
[edit] Analysis
 Before Normalization |
 After Normalization & Cleaning |
[edit] Samples/Quality Control
| Sample | Date Scanned | Source Link | Probe Variance Data | Artifact Mask | Quality Score |
|---|---|---|---|---|---|
| H157 Control group treatment. | 03/17/04 12:13:30 | GSM154492 | 
| 
| 93.496 0.22 % |
| H157 Low dose treatment group (100 nM) | 03/17/04 12:44:00 | GSM154493 | 
| 
| 96.1327 0.03 % |
| H157 High dose treatment group | 03/17/04 12:25:29 | GSM154494 | 
| 
| 95.2492 0.04 % |
| H1819 Control group treatment | 08/10/04 12:38:28 | GSM154495 | 
| 
| 93.786 0.07 % |
| H1819 Lose dose treatment group (100 nM) | 08/10/04 12:50:41 | GSM154496 | 
| 
| 96.9934 0.18 % |
| H1819 High dose treatment group (1000 nM) | 08/10/04 13:02:50 | GSM154497 | 
| 
| 97.3893 0.67 % |
| HBEC2 Control group treatment | 01/09/04 14:35:03 | GSM154498 | 
| 
| 91.3245 41.54 % |
